Crystallization and preliminary X-ray characterization of the Bacillus amyloliquefaciens YwrO enzyme

Journal Article · Sat Sep 01 04:00:00 EDT 2007 · Acta Crystallographica. Section F

DOI:https://doi.org/10.1107/S1744309107035816· OSTI ID:22360539

AbuKhader, Majed M. ^[1]; Heap, John ^[2]; De Matteis, Cristina I. ^[1]; Doughty, Stephen W. ^[3]; Minton, Nigel ^[2]; Paoli, Max ^[1]

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1. School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD (United Kingdom)
2. The Institute of Infection, Immunity and Inflammation, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD (United Kingdom)
3. Faculty of Health and Biological Sciences, School of Pharmacy, University of Nottingham Malaysia Campus, Jalan Broga, 43500 Semenyih, Selangor Darul Ehsan (Malaysia)

The novel bacterial nitroreductase YwrO from B. amyloliquefaciens has been crystallized in two different crystal forms. An initial molecular-replacement solution has been obtained using the mammalian NQO2 structure. CB1954 is an anticancer prodrug that is currently in clinical trials coupled with the Escherichia coli flavoenzyme nitroreductase (NTR) for use in directed-enzyme prodrug therapy (DEPT). The NTR enzyme is responsible for the conversion of the prodrug into a cytotoxic agent. The bifunctional alkylating agent produced by this bioactivation process leads to DNA damage and death of cancer cells. Recently, a novel flavoenzyme from Bacillus amyloliquefaciens, YwrO (Bam YwrO), was reported to be able to reduce CB1954 from its noncytotoxic form into its active form. The crystallization and preliminary X-ray diffraction analysis of two crystal forms of Bam YwrO are reported. The first crystal form is orthorhombic, with space group P22{sub 1}2{sub 1}, and diffracts X-rays to 2.18 Å resolution. The second crystal form is tetragonal, with space group P4{sub 1}, and diffracts X-rays to 3.4 Å. Determination of the Bam YwrO crystal structure will provide an understanding of the molecular recognition between this enzyme and the anticancer prodrug CB1954.

• OSTI ID: 22360539
• Journal Information: Acta Crystallographica. Section F, Journal Name: Acta Crystallographica. Section F Journal Issue: Pt 9 Vol. 63; ISSN ACSFCL; ISSN 1744-3091
• Country of Publication: United Kingdom
• Language: English

Related Subjects

75 CONDENSED MATTER PHYSICS
SUPERCONDUCTIVITY AND SUPERFLUIDITY
CONVERSION
CRYSTAL STRUCTURE
CRYSTALLIZATION
CRYSTALS
ESCHERICHIA COLI
MATHEMATICAL SOLUTIONS
NEOPLASMS
RESOLUTION
SOLUTIONS
SPACE GROUPS
X-RAY DIFFRACTION